The presence of cytomegalovirus (CMV) in
blood and semen is associated with higher levels of HIV DNA in blood,
investigators from the United States report in the online edition of Journal of Infectious Diseases. The
study involved gay men recently infected with HIV. The authors believe that CMV
replication may increase the reservoir of cells latently infected with HIV.
“This study demonstrated that presence of
CMV in PBMC [peripheral blood mononuclear cells] and in seminal plasma of HIV
infected ART-naïve MSM was associated with higher levels of proviral HIV DNA,”
write the authors. “It also found that simultaneous detectable CMV in semen and
PBMC was associated with the highest levels of HIV DNA in PBMC.”
Over 75% of HIV-positive gay men have at
least one herpes virus actively replicating in their semen and the most common
is CMV. Co-infection with CMV has been associated with accelerated HIV disease
progression and increased immune activation. Investigators from San Diego
hypothesised that it could also be an important factor in determining the size
of the reservoir of cells with latent HIV infection.
They therefore designed an observation
study involving 113 gay men recently infected with HIV. None were taking
antiretroviral therapy. Paired semen and blood samples were provided for
analysis. CMV DNA was quantified, as was proviral HIV DNA in PBMC, HIV viral
load and CD4 cell count.
The participants had been infected with HIV for
a median of 70 days at baseline. Median CD4 cell count at this time was 523
cells/mm3 and median blood plasma viral load was 50,000 copies/ml.
Approximately 46% of participants provided semen samples positive for CMV (median
peak viral load 4.52 log10 DNA copies/ml).
Just over half the cohort (52%) provided
paired longitudinal samples for analysis (median follow-up, 67 days).
Approximately a fifth had intermittent CMV shedding in semen and 10% had
intermittently detectable CMV DNA in PBMC. HIV DNA was detected in 91% of PBMC
Analysis of the entire cohort showed that
higher levels of HIV in DNA were associated with longer duration of HIV
infection, and the presence of CMV in PBMC.
However, blood plasma viral load and CD4
cell count were not associated with HIV DNA levels. The investigators were
surprised by this finding and performed two sub-analyses. The first excluded
participants with low-level HIV DNA. This revealed a positive association between
HIV viral load and HIV DNA (p = 0.01). The second excluded participants with an
estimated duration of infection of up to 120 days. This showed no association
between HIV viral load and HIV DNA. Nor was the presence of a sexually
transmitted infection at baseline associated with HIV DNA levels.
In multivariate analysis, the association between
CMV in PBMC and higher levels of HIV DNA in PBMC was significant (p = 0.05).
Participants with detectable CMV in both semen
and PBMC were more likely to have higher HIV DNA levels in PBMC than
individuals with undetectable CMV in both semen and PBMC (p = 0.02).
“This study provides important insights in
regard of one possible mechanism contributing to the establishment of the viral
reservoir during early HIV infection,” the investigators conclude. “Future
studies should determine if persistent CMV replication can be targeted as a
strategy to reduce the size of the latent HIV reservoir.”